In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 10 ( 2021-09-17)
Abstract:
Hepatitis B virus capsid assembly modulators (HBV CAMs) are promising, clinically validated therapeutic agents for the treatment of chronic hepatitis B (CHB). The safety, tolerability, and pharmacokinetic (PK) profiles of GST-HG141, a novel HBV CAM, were evaluated in healthy Chinese volunteers. This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 300, 400, or 500 mg) study comprising a food-effect investigation (300 mg) and a multiple-ascending-dose (MAD) (100 or 200 mg twice daily) study. GST-HG141 reached the maximum plasma concentration ( C max ) at 1.25 to 3.00 h (median T max ). The exposure exhibited a linear increase, while the mean half-life ( t 1/2 ) ranged from 13.096 h to 22.121 h. The exposure of GST-HG141 (300 mg) was higher after food intake by about 2.4-fold. In the MAD study, steady state was reached at around day 5, and the mean trough steady-state concentrations were 423 and 588 ng/ml for 50- and 100-mg cohorts, respectively. The ratios of GST-HG141 accumulation were 〈 1.5. GST-HG141 was well tolerated in healthy Chinese subjects. The rates of adverse events in the GST-HG141 cohort did not differ from those of the placebo cohort. GST-HG141 was tolerated in healthy Chinese subjects. The safety and PK profiles of GST-HG141 support the further evaluation of its efficacy in individuals with CHB. (This study has been registered in ClinicalTrials.gov under identifier NCT04536337.)
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01220-21
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2021
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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